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Clinically relevant chronic pain is often associated with functional impairment and behavioral depression as an "affective/motivational" sign of pain; however preclinical animal models of inflammatory and neuropathic pain often produce weak evidence of impaired function. We hypothesized that hindpaw mechanical stimulation produced by a requirement to rear on a textured "NOX" plate would punish operant responding in rats treated with intraplantar complete Freund's adjuvant (CFA, a model of inflammatory pain) or the chemotherapeutic paclitaxel (PTX, a model of neuropathic pain) and produce sustained pain-related depression of operant behavior. Male Sprague-Dawley rats were trained under a progressive-ratio (PR) schedule of food-maintained operant responding, then treated with CFA (100 µL in left hindpaw), PTX (2.0 mg/kg IP on alternate days for four total injections; 6.6 mg/kg IV on alternate days for three total injections), or saline vehicle. PR break points and mechanical thresholds for paw withdrawal from von Frey filaments were then tracked for 28 days. Subsequently, rats were tested with the opioid receptor antagonist naltrexone to assess latent sensitization and with the kappa opioid receptor (KOR) agonist U69593 to assess KOR function. CFA produced significant mechanical hypersensitivity for 3 weeks but decreased PR breakpoints for only 1 day. Both IP and IV PTX produced mechanical hypersensitivity for at least three weeks; however, only IV PTX decreased PR breakpoints, and this decrease was not alleviated by morphine. After recovery, naltrexone reinstated mechanical hypersensitivity in CFA- but not PTX-treated rats, and it did not reinstate depression of breakpoints in any group. U69593 dose-dependently decreased PR breakpoints in all groups with no difference between control vs. CFA/PTX groups. These results suggest that rearing on a textured NOX plate was not sufficient to punish operant responding in CFA- and PTX-treated rats despite the presence of sustained mechanical hypersensitivity. The rapid recovery of operant responding could not be attributed to latent sensitization, KOR downregulation, or behavioral tolerance. These results extend the range of conditions under which putative chronic pain manipulations produce weak evidence for depression of operant responding as a sign of the "affective/motivational" component of pain in rats.
Learn More >Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB).
Learn More >Coping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS).
Learn More >To compare the prevalence of psychiatric comorbidity between patients with complex regional pain syndrome (CRPS) of the hand and non-CRPS patients and to assess the association between biopsychosocial (BPS) complexity profiles and psychiatric comorbidity in a comparative study.
Learn More >Pathological stimuli or injury to the peripheral nervous system can trigger neuropathic pain with common clinical features such as allodynia and hypersensitivity. Although various studies have identified molecules or genes related to neuropathic pain, the essential components are still unclear. Therefore, in this study, we investigated the molecular and genetic factors related to neuropathic pain.
Learn More >Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition characterised by urinary urgency, frequency and pelvic pain, that significantly impacts the quality of life for ∼5% of women. Bladder sensation is coordinated by primary afferent sensory neurons that innervate the bladder wall, translating bladder stretch into signals that travel to the brain via the spinal cord. Whilst the pathophysiology of IC/BPS remains unknown, an increase in the permeability of the bladder urothelium has been proposed as an initiating cause. Here we experimentally increased bladder permeability and tracked bladder afferent sensitivity for up to 28 days. We found that one day after increasing bladder epithelial permeability with bladder infusion of protamine sulfate, mechanosensitive bladder afferents exhibited significant hypersensitivity to bladder filling. This mechanical hypersensitivity was characterised by significantly increased peak afferent firing rates and a decrease in the activation threshold of individual afferents. Bladder afferent hypersensitivity occurred in the absence of inflammation and changes in bladder muscle compliance, indicating a direct sensitisation of peripheral afferent endings. Bladder afferent mechanosensitive responses to distension returned to control levels by day 7 post-protamine sulfate treatment and remained at control levels at 28-days post-treatment. Here we demonstrate, contrary to the prevailing hypothesis, that increased bladder permeability alone does not induce chronic bladder afferent sensitisation. Whilst experimentally induced changes in bladder permeability are able to induce transient bladder afferent hypersensitivity in the absence of inflammation, highly regulated homeostatic mechanisms exist to rapidly repair the urothelial barrier and normalise bladder afferent mechanosensitivity. Together, these data suggest that additional pathophysiology is required to induce chronic bladder dysfunction.
Learn More >Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity.
Learn More >The visual network is crucially implicated in the pathophysiology of migraine. Several lines of evidence indicate that migraine is characterized by an altered visual cortex excitability both during and between attacks. Visual symptoms, the most common clinical manifestation of migraine aura, are likely the result of cortical spreading depression originating from the extrastriate area V3A. Photophobia, a clinical hallmark of migraine, is linked to an abnormal sensory processing of the thalamus which is converged with the non-image forming visual pathway. Finally, visual snow is an increasingly recognized persistent visual phenomenon in migraine, possibly caused by increased perception of subthreshold visual stimuli. Emerging research in non-invasive brain stimulation (NIBS) has vastly developed into a diversity of areas with promising potential. One of its clinical applications is the single-pulse transcranial magnetic stimulation (sTMS) applied over the occipital cortex which has been approved for treating migraine with aura, albeit limited evidence. Studies have also investigated other NIBS techniques, such as repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS), for migraine prophylaxis but with conflicting results. As a dynamic brain disorder with widespread pathophysiology, targeting migraine with NIBS is challenging. Furthermore, unlike the motor cortex, evidence suggests that the visual cortex may be less plastic. Controversy exists as to whether the same fundamental principles of NIBS, based mainly on findings in the motor cortex, can be applied to the visual cortex. This review aims to explore existing literature surrounding NIBS studies on the visual system of migraine. We will first provide an overview highlighting the direct implication of the visual network in migraine. Next, we will focus on the rationale behind using NIBS for migraine treatment, including its effects on the visual cortex, and the shortcomings of currently available evidence. Finally, we propose a broader perspective of how novel approaches, the concept of brain networks and the integration of multimodal imaging with computational modeling, can help refine current NIBS methods, with the ultimate goal of optimizing a more individualized treatment for migraine.
Learn More >In this observational study, using the Global Burden of Disease and Risk Factors Study, we aimed to (i) report the magnitude of health loss due to non-communicable neurological disorders in the USA in 2017 by sex, age, years and States and (ii) to identify non-communicable neurological disorders attributable environmental, metabolic and behavioural risk factors. We provide estimates of the burden of non-communicable neurological disorders by reporting disability-adjusted life-years and their trends from 1990 to 2017 by age and sex in the USA. The non-communicable neurological disorders include migraines, tension-type headaches, multiple sclerosis, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, motor neuron diseases and other neurological disorders. In 2017, the global burdens of non-communicable neurological disorders were 1444.41 per 100 000, compared to the USA burden of 1574.0. Migraine was the leading age-standardized disability-adjusted life-years 704.7 per 100 000, with Alzheimer's disease and other dementias (41.8.7), and epilepsy (123.8) taking the second and third places, respectively. Between 1990 and 2017, the age-standardized disability-adjusted life-years rates for aggregate non-communicable neurological disorders relative to all cause increased by 3.42%. More specifically, this value for motor neuron diseases, Parkinson's disease and multiple sclerosis increase by 20.9%, 4.0%, 2.47%, 3.0% and 1.65%, respectively. In 2017, the age-standardized disability-adjusted life-years rates for the aggregate non-communicable neurological disorders was significantly higher in females than the males (1843.5 versus 1297.3 per 100 000), respectively. The age-standardized disability-adjusted life-years rates for migraine were the largest in both females (968.8) and males were (432.5) compared to other individual non-communicable neurological disorders. In the same year, the leading non-communicable neurological disorders age-standardized disability-adjusted life-years rates among children ≤9 was epilepsy (216.4 per 100 000). Among the adults aged 35-60 years, it was migraine (5792.0 per 100 000), and among the aged 65 and above was Alzheimer's disease and other dementias (78 800.1 per 100 000). High body mass index, smoking, high fasting plasma glaucous and alcohol use were the attributable age-standardized disability-adjusted life-years risks for aggregate and individual non-communicable neurological disorders. Despite efforts to decrease the burden of non-communicable neurological disorders in the USA, they continue to burden the health of the population. Children are most vulnerable to epilepsy-related health burden, adolescents and young adults to migraine, and elderly to Alzheimer's disease and other dementias and epilepsy. In all, the most vulnerable populations to non-communicable neurological disorders are females, young adults and the elderly.
Learn More >Legalization of cannabis encourages the development of specific cultivars to treat disease such as neuropathic pain. Because of the large number of cultivars, it is necessary to prioritize extracts before proceeding to clinical trials.
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